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Abstract(s)
A Esquizofrenia é uma doença psiquiátrica complexa e até aos dias de hoje sem cura conhecida. O espetro de sintomas é vasto e heterogéneo para os vários doentes, incluindo alucinações e delírios, reduzida expressão emocional/verbal e défices na cognição. Estes sintomas causam um grande défice no funcionamento normal do indivíduo. Tipicamente a doença surge no início da idade adulta, frequentemente com um período prodrómico acompanhado por declínio a nível social ou cognitivo. As causas da Esquizofrenia não estão totalmente estabelecidas. Existe bastante evidência da importância da componente genética, que é composta por variantes comuns de baixo risco e certas variantes genéticas raras conferindo maior risco. A nível ambiental foram identificados muitos fatores que podem também contribuir para o desenvolvimento da Esquizofrenia. Entre eles encontram-se complicações a nível pré-natal, idade dos pais, trauma na infância, migração e consumo de canábis. A nível da fisiopatologia, a teoria da dopamina serviu como base para o desenvolvimento da terapêutica farmacológica. Contudo, existe clara evidência do papel de desregulações a nível de outros sistemas de neurotransmissores cerebrais, proeminentemente, o glutamato e a serotonina. A pesquisa científica parece apontar para uma contribuição integrada destes sistemas.
O tratamento da Esquizofrenia é efetuado com fármacos antipsicóticos. Embora eficazes contra sintomas de psicose, os antipsicóticos apresentam pouco efeito a nível dos sintomas negativos e cognitivos, sintomas particularmente associados a um mau prognóstico e maior morbilidade. O mecanismo transversal à maioria destes fármacos é o antagonismo D2 do recetor da dopamina a nível da via dopaminérgica mesolímbica. Antipsicóticos de primeira geração, embora com eficácia semelhante aos de segunda geração ou atípicos, produzem efeitos motores
muito disruptivos, pelo que os antipsicóticos atípicos, embora associados a alterações metabólicas, são normalmente preferidos. As terapias não farmacológicas podem ser um importante aliado ao tratamento farmacológico, tentando melhorar o aspeto social, cognitivo e a forma como a pessoa lida com a doença. Fármacos com mecanismo de ação distinto do antagonismo D2 têm vindo a ser estudados na esperança de futuramente se conseguir um tratamento eficaz a nível de sintomas negativos e cognitivos e também mitigar os efeitos adversos das terapêuticas disponíveis no presente.
Schizophrenia is a complex psychiatric illness and, to date, there is no known cure. The spectrum of symptoms is vast and heterogeneous for different patients, including hallucinations and delusions, reduced emotional/verbal expression and cognitive deficits. These symptoms cause a great deficit in the normal functioning of the individual. Typically, the disease appears in early adulthood, often with a prodromal period accompanied by social or cognitive decline. The causes of Schizophrenia are not fully established. There is considerable evidence of the importance of the genetic component, which is composed of common low-risk variants and certain rare genetic variants conferring greater risk. At the environmental level, many factors have been identified that may also contribute to the development of Schizophrenia. These include prenatal complications, parental age, childhood trauma, migration and cannabis use. In terms of pathophysiology, the dopamine theory served as a basis for the development of pharmacological therapy. However, there is clear evidence for the role of dysregulations in other brain neurotransmitter systems, prominently, glutamate and serotonin. Scientific research seems to point to an integrated contribution of these systems. Schizophrenia is treated with antipsychotic drugs. Although effective against symptoms of psychosis, antipsychotics have little effect on negative and cognitive symptoms, symptoms particularly associated with poor prognosis and increased morbidity. The mechanism transversal to most of these drugs is the D2 antagonism of the dopamine receptor at the level of the mesolimbic dopaminergic pathway. First-generation antipsychotics, although with similar efficacy to second-generation or atypical antipsychotics, produce very disruptive motor effects, so atypical antipsychotics, although associated with metabolic changes, are usually preferred. Non-pharmacological therapies can be an important ally to pharmacological treatment, trying to improve the social, cognitive aspect and the way the person deals with the disease. Drugs with a different mechanism of action of D2 antagonism have been studied in hope of achieving an effective treatment in the future in terms of negative and cognitive symptoms and also mitigating the adverse effects of currently available therapies.
Schizophrenia is a complex psychiatric illness and, to date, there is no known cure. The spectrum of symptoms is vast and heterogeneous for different patients, including hallucinations and delusions, reduced emotional/verbal expression and cognitive deficits. These symptoms cause a great deficit in the normal functioning of the individual. Typically, the disease appears in early adulthood, often with a prodromal period accompanied by social or cognitive decline. The causes of Schizophrenia are not fully established. There is considerable evidence of the importance of the genetic component, which is composed of common low-risk variants and certain rare genetic variants conferring greater risk. At the environmental level, many factors have been identified that may also contribute to the development of Schizophrenia. These include prenatal complications, parental age, childhood trauma, migration and cannabis use. In terms of pathophysiology, the dopamine theory served as a basis for the development of pharmacological therapy. However, there is clear evidence for the role of dysregulations in other brain neurotransmitter systems, prominently, glutamate and serotonin. Scientific research seems to point to an integrated contribution of these systems. Schizophrenia is treated with antipsychotic drugs. Although effective against symptoms of psychosis, antipsychotics have little effect on negative and cognitive symptoms, symptoms particularly associated with poor prognosis and increased morbidity. The mechanism transversal to most of these drugs is the D2 antagonism of the dopamine receptor at the level of the mesolimbic dopaminergic pathway. First-generation antipsychotics, although with similar efficacy to second-generation or atypical antipsychotics, produce very disruptive motor effects, so atypical antipsychotics, although associated with metabolic changes, are usually preferred. Non-pharmacological therapies can be an important ally to pharmacological treatment, trying to improve the social, cognitive aspect and the way the person deals with the disease. Drugs with a different mechanism of action of D2 antagonism have been studied in hope of achieving an effective treatment in the future in terms of negative and cognitive symptoms and also mitigating the adverse effects of currently available therapies.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2022, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Esquizofrenia Psicose Sintomas negativos Sistema dopaminérgico Antipsicóticos Mestrado integrado - 2022